Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels
- University of Chicago, United States
- University of Arizona, United States
Abstract
In Shaker K+ channels, the S4-S5 linker couples the voltage sensor (VSD) and pore domain (PD). Another coupling mechanism is revealed using two W434F-containing channels: L361R:W434F and L366H:W434F. In L361R:W434F, W434F affects the L361R VSD seen as a shallower Q-V curve that crosses the G-V. In L366H:W434F, L366H relieves the W434F effect converting a non-conductive channel in a conductive one. We report a chain of residues connecting the VSD (S4) to the selectivity filter (SF) in the PD of an adjacent subunit as the molecular basis for voltage-sensor selectivity filter gate (VS-SF) coupling. Single alanine substitutions in this region (L409A, S411A, S412A or F433A) are enough to disrupt the VS-SF coupling, shown by the absence of Q-V and G-V crossing in L361R:W434F mutant and by the lack of ionic conduction in the L366H:W434F mutant. This residue chain defines a new coupling between the VSD and the PD in voltage-gated channels.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Francisco Bezanilla
Funding
National Institutes of Health (R01-GM030376)
- Francisco Bezanilla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institution of animal care and use committee (IACUC) protocols (#71745) of the University of Chicago.
Copyright
© 2021, Bassetto et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels
eLife 10:e63077.
https://doi.org/10.7554/eLife.63077
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